tbuckley/cabot-search huggingface dataset:
Insights and opportunities for deep brain stimulation as a brain circuit intervention
Authors: Wolf-Julian Neumann, Andreas Horn, Andrea A. Kühn
Journal: Trends in Neurosciences (2023)

Deep brain stimulation (DBS) is an effective treatment and has provided unique insights into the dynamic circuit architecture of brain disorders. This Review illustrates our current understanding of the pathophysiology of movement disorders and their underlying brain circuits that are modulated with DBS. It proposes principles of pathological network synchronization patterns like beta activity (13–35 Hz) in Parkinson's disease. We describe alterations from microscale including local synaptic activity via modulation of mesoscale hypersynchronization to changes in whole-brain macroscale connectivity. Finally, an outlook on advances for clinical innovations in next-generation neurotechnology is provided: from preoperative connectomic targeting to feedback controlled closed-loop adaptive DBS as individualized network-specific brain circuit interventions.
Clinical impact of syndromic molecular point-of-care testing for gastrointestinal pathogens in adults hospitalised with suspected gastroenteritis (GastroPOC): a pragmatic, open-label, randomised controlled trial
Authors: Nathan J Brendish, Kate R Beard, Ahalya K Malachira, Alex R Tanner, Langizya Sanga-Nyirongo, Markus Gwiggner, J R Fraser Cummings, Helen E Moyses, Tristan W Clark
Journal: The Lancet Infectious Diseases (2023)
Off-label is not always off-evidence: authorising paediatric indications for old medicines
Authors: Saskia N de Wildt, Ivan Foeldvari, Angeliki Siapkara, Pirkko Lepola, Berit Kriström, Lucia Ruggieri, Irmgard Eichler, Gunter F Egger
Journal: The Lancet Child & Adolescent Health (2023)
Mental health and psychosocial support in humanitarian settings: research priorities for 2021–30
Authors: Wietse A Tol, PhuongThao D Le, Sarah L Harrison, Ananda Galappatti, Jeannie Annan, Florence K Baingana, Theresa S Betancourt, Cecile Bizouerne, Julian Eaton, Michelle Engels, Zeinab Hijazi, Rebecca R Horn, Mark J D Jordans, Brandon A Kohrt, Phiona Koyiet, Catherine Panter-Brick, Michael Pluess, Atif Rahman, Derrick Silove, Mark Tomlinson, José Miguel Uribe-Restrepo, Peter Ventevogel, Inka Weissbecker, Alastair Ager, Mark van Ommeren
Journal: The Lancet Global Health (2023)
Transgenic angiotensin-converting enzyme 2 overexpression in the rat vasculature protects kidneys from ageing-induced injury
Authors: Antonia Maria Sanad, Fatimunnisa Qadri, Elena Popova, André Felipe Rodrigues, Timm Heinbokel, Susanna Quach, Angela Schulz, Sebastian Bachmann, Reinhold Kreutz, Natalia Alenina, Michael Bader
Journal: Kidney International (2023)
Effect of viral storm in patients admitted to intensive care units with severe COVID-19 in Spain: a multicentre, prospective, cohort study
Authors: Jesús F Bermejo-Martin, Nadia García-Mateo, Anna Motos, Salvador Resino, Luis Tamayo, Pablo Ryan Murua, Elena Bustamante-Munguira, Elena Gallego Curto, Alejandro Úbeda-Iglesias, María Del Carmen de la Torre, Ángel Estella, Sandra Campos-Fernández, Ignacio Martínez Varela, Felipe Pérez-García, Lorenzo Socias, Juan López Messa, Pablo Vidal-Cortés, Víctor Sagredo Meneses, Milagros González-Rivera, Nieves Carbonell, David de Gonzalo-Calvo, María Cruz Martín Delgado, Luis Jorge Valdivia, Caridad Martín-López, Ruth Noemí Jorge García, Emilio Maseda, Ana Loza-Vázquez, David J Kelvin, Ferrán Barbé, Antoni Torres
Journal: The Lancet Microbe (2023)
Hydrochlorothiazide use and risk of keratinocyte carcinoma and melanoma: A multisite population-based cohort study
Authors: Laurent Azoulay, Audray St-Jean, Matthew Dahl, Jacqueline Quail, Wusiman Aibibula, James M. Brophy, An-Wen Chan, Lauren Bresee, Greg Carney, Sherif Eltonsy, Hala Tamim, J. Michael Paterson, Robert W. Platt
Journal: Journal of the American Academy of Dermatology (2023)
Molecular testing in suspected infectious diarrhoea—the value of negative results
Authors: Mark H Wilcox
Journal: The Lancet Infectious Diseases (2023)

Molecular testing for the detection of gastrointestinal pathogens is not new, and yet its potential to benefit patient management remains underexplored. The multiplicity of tests and varied numbers of target pathogens complicates their assessment. Molecular tests are rapid (results usually in 1–4 h), typically expand the range of detectable potential pathogens, can be laboratory-based or near-to-patient, but are relatively costly because of consumable and equipment needs. Culture-based results are much slower (at least the day after a sample reaches the laboratory) and require skilled expertise to process, so increasing their overall cost.
Circulating tumor DNA analysis of the phase III VOYAGER trial: KIT mutational landscape and outcomes in patients with advanced gastrointestinal stromal tumor treated with avapritinib or regorafenib
Authors: C. Serrano, S. Bauer, D. Gómez-Peregrina, Y.-K. Kang, R.L. Jones, P. Rutkowski, O. Mir, M.C. Heinrich, W.D. Tap, K. Newberry, A. Grassian, H. Shi, S. Bialick, P. Schöffski, M.A. Pantaleo, M. von Mehren, J.C. Trent, S. George
Journal: Annals of Oncology (2023)
Multifunctional two-component in-situ hydrogel for esophageal submucosal dissection for mucosa uplift, postoperative wound closure and rapid healing
Authors: Xiong-Xin Lei, Juan-Juan Hu, Chen-Yu Zou, Yan-Lin Jiang, Long-Mei Zhao, Xiu-Zhen Zhang, Ya-Xing Li, An-Ni Peng, Yu-Ting Song, Li-Ping Huang, Jesse Li-Ling, Hui-Qi Xie
Journal: Bioactive Materials (2023)

Endoscopic submucosal dissection (ESD) for gastrointestinal tumors and premalignant lesions needs submucosal fluid cushion (SFC) for mucosal uplift before dissection, and wound care including wound closure and rapid healing postoperatively. Current SFC materials as well as materials and/or methods for post-ESD wound care have single treatment effect and hold corresponding drawbacks, such as easy dispersion, short duration, weak hemostasis and insufficient repair function. Thus, designing materials that can serve as both SFC materials and wound care is highly desired, and remains a challenge. Herein, we report a two-component in-situ hydrogel prepared from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl-chitosan, which gelated mainly based on "click" chemistry and Schiff base reaction. The hydrogels showed short gelation time, outstanding tissue adhesion, favorable hemostatic properties, and good biocompatibility. A rat subcutaneous ultrasound model confirmed the ability of suitable mucosal uplift height and durable maintenance time of AM solution. The in vivo/in vitro rabbit liver hemorrhage model demonstrated the effects of hydrogel in rapid hemostasis and prevention of delayed bleeding. The canine esophageal ESD model corroborated that the in-situ hydrogel provided good mucosal uplift and wound closure effects, and significantly accelerated wound healing with accelerating re-epithelization and ECM remodeling post-ESD. The two-component in-situ hydrogels exhibited great potential in gastrointestinal tract ESD.
Reply to the letter regarding “Palliative care and end-of-life care in adults with malignant brain tumors”
Authors: Johan A F Koekkoek, Pim B van der Meer, Tobias Walbert
Journal: Neuro-Oncology (2023)

We thank Dr. Röttgering et al. for sharing their thoughts on our guidelines on palliative care and end-of-life care in brain tumor patients.1 In this consensus paper we aimed to provide an overview of symptom management and other palliative care interventions by updating the literature as previously published in the EANO 2017 guideline on palliative care in adults with glioma. To improve symptomatic treatment in brain tumor patients, Röttgering et al. recommend using a network-based approach for a comparative analysis of symptoms between brain tumor patients and patients with other diseases. Network analysis may help to find correlations between symptoms across different conditions that cannot solely be attributed to a specific disease or its treatment. Fatigue is one of the core symptoms in all cancer patients that correlate directly with other symptoms like emotional symptoms, cognitive symptoms, appetite loss, dyspnea, and pain.2 As the authors rightly point out, to address fatigue, patients with a brain tumor may benefit from interventions that have been studied in fatigued patients with other conditions.
Risk assessment of human mpox infections: retrospective cohort study
Authors: Roy Zucker, Gil Lavie, Yael Wolff-Sagy, Noa Gur-Arieh, Hila Markovits, Wiessam Abu-Ahmad, Erez Battat, Noga Ramot, Tanya Beckenstein, Guy Carmeli, Avner Mark-Amir, Gal Wagner-Kolasko, Amos Edry, Hadar Duskin-Bitan, Shlomit Yaron, Alon Peretz, Ariel Hammerman, Doron Netzer, Ronen Arbel
Journal: Clinical Microbiology and Infection (2023)
Prospective Analysis Reveals Associations between Carbohydrate Intakes, Genetic Predictors of Short-Chain Fatty Acid Synthesis, and Colorectal Cancer Risk
Authors: Cody Z. Watling, Rebecca K. Kelly, Neil Murphy, Marc Gunter, Carmen Piernas, Kathryn E. Bradbury, Julie A. Schmidt, Timothy J. Key, Aurora Perez-Cornago
Journal: Cancer Research (2023)

Abstract Whole grain and fiber intakes may decrease the risk of colorectal cancer. The interplay between host genetic factors, colonization of specific bacteria, production of short-chain fatty acids (SCFA), and intake of whole grains and fiber could alter the protective role of carbohydrates against colorectal cancer. Here, we assessed intakes of types and sources of carbohydrates in 114,217 UK Biobank participants with detailed dietary data (2–5 24-hour dietary assessments), and a host polygenic score (PGS) was applied to categorize participants as high or low for intraluminal microbial SCFA production, namely, butyrate and propionate. Multivariable Cox proportional hazards models were used to determine the associations of carbohydrates and SCFA with colorectal cancer incidence. During a median follow-up of 9.4 years, 1,193 participants were diagnosed with colorectal cancer. Risk was inversely associated with intakes of non-free sugar and whole grain fiber. Evidence of heterogeneity was observed by the butyrate PGS; consuming higher amounts of whole grain starch was only associated with a lower risk of colorectal cancer in those with predicted high SCFA production. Similarly, in additional analyses utilizing the larger UK Biobank cohort (N = 343,621) with less detailed dietary assessment, only individuals with a high genetically predicted butyrate production had a lower risk of colorectal cancer per 5 g/day intake of bread and cereal fiber. This study suggests that colorectal cancer risk varies by intake of carbohydrate types and sources, and the impact of whole grain intake may be modified by SCFA production. Significance: Prospective population-level analyses provide evidence supporting the importance of butyrate production in reduction of colorectal cancer risk by whole grain consumption.
CD16+ Macrophages: An Emerging Biomarker for Combined CTLA-4 and PD-1 Blockade
Authors: James W. Smithy, Jason J. Luke
Journal: Clinical Cancer Research (2023)

Summary In a retrospective analysis of patients with unresectable melanoma, higher pretreatment tissue densities of CD16+ macrophages were associated with clinical benefit from combined CTLA-4 and PD-1 blockade. With further validation, this biomarker could serve as a tool in selecting between immune checkpoint inhibitor regimens. See related article by Lee et al., p. 2513
Lung Recruitment Assessed by Electrical Impedance Tomography (RECRUIT): A Multicenter Study of COVID-19 Acute Respiratory Distress Syndrome
Authors: Annemijn H. Jonkman, Glasiele C. Alcala, Bertrand Pavlovsky, Oriol Roca, Savino Spadaro, Gaetano Scaramuzzo, Lu Chen, Jose Dianti, Mayson L. de A. Sousa, Michael C. Sklar, Thomas Piraino, Huiqing Ge, Guang-Qiang Chen, Jian-Xin Zhou, Jie Li, Ewan C. Goligher, Eduardo Costa, Jordi Mancebo, Tommaso Mauri, Marcelo Amato, Laurent J. Brochard, Tobias Becher, Giacomo Bellani, Francois Beloncle, Gilda Cinnella, Carla Fornari, Inéz Frerichs, Claude Guerin, Ahmed Mady, Fabiana Madotto, Alain Mercat, Ibrahim Nagwa, Stefano Nava, Paolo Navalesi, Elena Spinelli, Daniel Talmor
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Defining lung recruitability is needed for safe positive end-expiratory pressure (PEEP) selection in mechanically ventilated patients. However, there is no simple bedside method including both assessment of recruitability and risks of overdistension as well as personalized PEEP titration.
Clinicopathologic, Genomic, and Immunophenotypic Landscape of <i>ATM</i> Mutations in Non–Small Cell Lung Cancer
Authors: Biagio Ricciuti, Arielle Elkrief, Joao Alessi, Xinan Wang, Yvonne Li, Hersh Gupta, Daniel M. Muldoon, Arrien A. Bertram, Federica Pecci, Giuseppe Lamberti, Alessandro Di Federico, Adriana Barrichello, Victor R. Vaz, Malini Gandhi, Elinton Lee, Geoffrey I. Shapiro, Hyesun Park, Mizuki Nishino, James Lindsay, Kristen D. Felt, Bijaya Sharma, Andrew D. Cherniack, Scott Rodig, Daniel R. Gomez, Narek Shaverdian, Mehrdad Rakaee, Chaitanya Bandlamudi, Marc Ladanyi, Pasi A. Janne, Adam J. Schoenfeld, Lynette M. Sholl, Mark M. Awad, Michael L. Cheng
Journal: Clinical Cancer Research (2023)

Abstract Purpose: ATM is the most commonly mutated DNA damage and repair gene in non–small cell lung cancer (NSCLC); however, limited characterization has been pursued. Experimental Design: Clinicopathologic, genomic, and treatment data were collected for 5,172 patients with NSCLC tumors which underwent genomic profiling. ATM IHC was performed on 182 NSCLCs with ATM mutations. Multiplexed immunofluorescence was performed on a subset of 535 samples to examine tumor-infiltrating immune cell subsets. Results: A total of 562 deleterious ATM mutations were identified in 9.7% of NSCLC samples. ATM-mutant (ATMMUT) NSCLC was significantly associated with female sex (P = 0.02), ever smoking status (P &amp;lt; 0.001), non-squamous histology (P = 0.004), and higher tumor mutational burden (DFCI, P &amp;lt; 0.0001; MSK, P &amp;lt; 0.0001) compared with ATM–wild-type (ATMWT) cases. Among 3,687 NSCLCs with comprehensive genomic profiling, co-occurring KRAS, STK11, and ARID2 oncogenic mutations were significantly enriched among ATMMUT NSCLCs (Q &amp;lt; 0.05), while TP53 and EGFR mutations were enriched in ATMWT NSCLCs. Among 182 ATMMUT samples with ATM IHC, tumors with nonsense, insertions/deletions, or splice site mutations were significantly more likely to display ATM loss by IHC (71.4% vs. 28.6%; P &amp;lt; 0.0001) compared with tumors with only predicted pathogenic missense mutations. Clinical outcomes to PD-(L)1 monotherapy (N = 1,522) and chemo-immunotherapy (N = 951) were similar between ATMMUT and ATMWT NSCLCs. Patients with concurrent ATM/TP53 mutations had significantly improved response rate and progression-free survival with PD-(L)1 monotherapy. Conclusions: Deleterious ATM mutations defined a subset of NSCLC with unique clinicopathologic, genomic, and immunophenotypic features. Our data may serve as resource to guide interpretation of specific ATM mutations in NSCLC.
ECM‐Like Adhesive Hydrogel for the Regeneration of Large Corneal Stromal Defects
Authors: Fuyan Wang, Wei Zhang, Yujie Qiao, Depeng Shi, Lizhi Hu, Jun Cheng, Jingyi Wu, Long Zhao, Donfang Li, Weiyun Shi, Lixin Xie, Qingjun Zhou
Journal: Advanced Healthcare Materials (2023)

The repair of large-diameter corneal stroma defects is a major clinical problem. Although some studies have attempted to use hydrogels to repair corneal damage, most of these hydrogels can only be used for focal stromal defects that are ≤3.5 mm in diameter due to poor hydrogel adhesion. Here, a photocurable adhesive hydrogel that mimics the extracellular matrix (ECM) with regard to composition for repairing 6 mm-diameter corneal stromal defects in rabbits is investigated. This ECM-like adhesive can be rapidly cured after light exposure, with high light transmittance and good mechanical properties. More importantly, this hydrogel maintains the viability and adhesion of cornea-derived cells and promotes their migration in vitro in 2D and 3D culture environments. Proteomics analysis confirms that the hydrogel promotes cell proliferation and ECM synthesis. Furthermore, in rabbit corneal stromal defect repair experiments, it is proven by histological and proteomic analysis that this hydrogel can effectively promote corneal stroma repair, reduce scar formation, and increase corneal stromal-neural regeneration at the six months follow-up. This work demonstrates the great application of ECM-like adhesive hydrogels for the regeneration of large-diameter corneal defects.
Annotating and prioritizing human non-coding variants with RegulomeDB v.2
Authors: Shengcheng Dong, Nanxiang Zhao, Emma Spragins, Meenakshi S. Kagda, Mingjie Li, Pedro Assis, Otto Jolanki, Yunhai Luo, J. Michael Cherry, Alan P. Boyle, Benjamin C. Hitz
Journal: Nature Genetics (2023)
IRF7 and UNC93B1 variants in an infant with recurrent herpes simplex virus infection
Authors: Megan H. Tucker, Wei Yu, Heather Menden, Sheng Xia, Carl F. Schreck, Margaret Gibson, Daniel Louiselle, Tomi Pastinen, Nikita Raje, Venkatesh Sampath
Journal: Journal of Clinical Investigation (2023)

Neonatal herpes simplex virus (HSV) infection is a devastating disease with substantial morbidity and mortality. The genetic basis of susceptibility to HSV in neonates remains undefined. We investigated a male infant with neonatal skin/eye/mouth (SEM) HSV1 disease who had complete recovery after acyclovir but developed HSV1 encephalitis at 1 year of age. Immune work up showed an anergic peripheral blood monocyte cytokine (PBMC) response to TLR3 stimulation but no other TLRs. Exome sequencing identified rare missense variants in IRF7 and UNC93B1. PBMC single cell RNA sequencing done during childhood revealed decreased expression of several innate immune genes and a repressed TLR3 pathway signature at baseline in several immune cell populations, including CD14 monocytes. Functional studies in fibroblasts and THP-1 showed that both variants individually suppressed TLR3-driven IRF3 promoter activity and type I interferon response in vitro. Furthermore, fibroblasts expressing the IRF7 and UNC93B1 variants had higher intracellular viral titers with blunting of the type I interferon response upon HSV1 challenge. This study reports an infant with recurrent HSV1 disease complicated by encephalitis associated with deleterious variants in IRF7 and UNC93B1 genes. Our results suggest that TLR3 pathway mutations may predispose neonates to recurrent severe HSV.
DPP4 inhibition impairs senohemostasis to improve plaque stability in atherosclerotic mice
Authors: Allison B. Herman, Dimitrios Tsitsipatis, Carlos Anerillas, Krystyna Mazan-Mamczarz, Angelica E. Carr, Jordan M. Gregg, Mingyi Wang, Jing Zhang, Marc Michel, Charnae’ A. Henry-Smith, Sophia C. Harris, Rachel Munk, Jennifer L. Martindale, Yulan Piao, Jinshui Fan, Julie A. Mattison, Supriyo De, Kotb Abdelmohsen, Robert W. Maul, Toshiko Tanaka, Ann Zenobia Moore, Megan E. DeMouth, Simone Sidoli, Luigi Ferrucci, Yie Liu, Rafael de Cabo, Edward G. Lakatta, Myriam Gorospe
Journal: Journal of Clinical Investigation (2023)

Senescent vascular smooth muscle cells (VSMCs) accumulate in the vasculature with age and tissue damage and secrete factors that promote atherosclerotic plaque vulnerability and disease. Here, we report increased levels and activity of dipeptidyl peptidase 4 (DPP4), a serine protease, in senescent VSMCs. Analysis of the conditioned media from senescent VSMCs revealed a unique senescence-associated secretory phenotype (SASP) signature comprising many complement and coagulation factors; silencing or inhibiting DPP4 reduced these factors and increased cell death. Serum samples from persons with high risk for cardiovascular disease contained high levels of DPP4-regulated complement and coagulation factors. Importantly, DPP4 inhibition reduced senescent cell burden and coagulation and improved plaque stability, while single-cell resolution of senescent VSMCs reflected the senomorphic and senolytic effects of DPP4 inhibition in murine atherosclerosis. We propose that DPP4-regulated factors could be exploited therapeutically to reduce senescent cell function, reverse senohemostasis, and improve vascular disease.
RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer
Authors: Amanda J. Compadre, Lillian N. van Biljon, Mark C. Valentine, Alba Llop-Guevara, Emily Graham, Bisiayo Fashemi, Andrea Herencia-Ropero, Emilee N. Kotnik, Isaac Cooper, Shariska P. Harrington, Lindsay M. Kuroki, Carolyn K. McCourt, Andrea R. Hagemann, Premal H. Thaker, David G. Mutch, Matthew A. Powell, Lulu Sun, Nima Mosammaparast, Violeta Serra, Peinan Zhao, Elena Lomonosova, Dineo Khabele, Mary M. Mullen
Journal: Clinical Cancer Research (2023)

To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples.
Learning Rat-Like Behavioral Interaction Using a Small-Scale Robotic Rat
Authors: Hongzhao Xie, Zihang Gao, Guanglu Jia, Shingo Shimoda, Qing Shi
Journal: Cyborg and Bionic Systems (2023)

In this paper, we propose a novel method for emulating rat-like behavioral interactions in robots using reinforcement learning. Specifically, we develop a state decision method to optimize the interaction process among 6 known behavior types that have been identified in previous research on rat interactions. The novelty of our method lies in using the temporal difference (TD) algorithm to optimize the state decision process, which enables the robots to make informed decisions about their behavior choices. To assess the similarity between robot and rat behavior, we use Pearson correlation. We then use TD-λ to update the state value function and make state decisions based on probability. The robots execute these decisions using our dynamics-based controller. Our results demonstrate that our method can generate rat-like behaviors on both short- and long-term timescales, with interaction information entropy comparable to that between real rats. Overall, our approach shows promise for controlling robots in robot-rat interactions and highlights the potential of using reinforcement learning to develop more sophisticated robotic systems.